Cytokines and protooncogenes are critical modulators of cellular function, viability, differentiation and communication. As such, cytokines are now being used in the treatment of many diseases including cancer, autoimmunity, anemia and renal failure. It is likely that in the near future drugs capable of interfering with protooncogenes will also find clinical use. The long term objective of this project is to identify new cytokines and protooncogenes by a novel affinity chromatographic technique. Using this process, we have constructed several cDNA libraries which are substantially enriched for cytokine and protooncogene cDNAs. Thirty-five percent of randomly screened cDNAs from this library code for known cytokines or protooncogenes while an equal percentage are unique without homology to known human mRNAs. The aims of this Phase I project are to 1). identify all novel cDNAs within the library by partial nucleotide sequencing and database search and 2). clone the corresponding full-length cDNAs from tissue specific cDNA libraries. If we are successful, we will apply for Phase 2 funds to construct new libraries from additional cell and tissue sources, characterize the functionality of our novel cytokines and protooncogenes and begin the commercialization process for these important new molecules with established pharmaceutical companies. PROPOSED COMMERCIAL APPLICATION: Cytokines and protooncogenes are implicated in numerous diseases, including cancer. Symphony has developed a novel method of cloning members of these gene families based upon their post- transcriptional regulatory features. The cloning of novel cytokines and protooncogenes will provide new targets for therapeutic intervention. Symphony has also developed a drug screening program targeting post-transcriptional interactions for which these newly identified genes would represent potential targets.